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Rejection of intestinal allotransplants is driven by memory T helper type 17 immunity and responds to infliximab.
Kroemer, Alexander; Belyayev, Leonid; Khan, Khalid; Loh, Katrina; Kang, Jiman; Duttargi, Anju; Dhani, Harmeet; Sadat, Mohammed; Aguirre, Oswaldo; Gusev, Yuriy; Bhuvaneshwar, Krithika; Kallakury, Bhaskar; Cosentino, Christopher; Houlihan, Brenna; Diaz, Jamie; Moturi, Sangeetha; Yazigi, Nada; Kaufman, Stuart; Subramanian, Sukanya; Hawksworth, Jason; Girlanda, Raffaelle; Robson, Simon C; Matsumoto, Cal S; Zasloff, Michael; Fishbein, Thomas M.
Afiliação
  • Kroemer A; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Belyayev L; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Khan K; Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
  • Loh K; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Kang J; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Duttargi A; Department of Gastroenterology, Hepatology and Nutrition, Children's National Medical Center, Washington, District of Columbia, USA.
  • Dhani H; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Sadat M; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Aguirre O; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Gusev Y; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Bhuvaneshwar K; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Kallakury B; Innovation Center for Biomedical Informatics (ICBI), Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Cosentino C; Innovation Center for Biomedical Informatics (ICBI), Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Houlihan B; Department of Pathology, MedStar Georgetown University Hospital, Washington, District of Columbia, USA.
  • Diaz J; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Moturi S; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Yazigi N; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Kaufman S; Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
  • Subramanian S; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Hawksworth J; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Girlanda R; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Robson SC; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Matsumoto CS; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
  • Zasloff M; Department of Surgery, Walter Reed National Military Medical Center, Bethesda, Maryland, USA.
  • Fishbein TM; The Center for Translational Transplant Medicine, MedStar Georgetown Transplant Institute, MedStar Georgetown University Hospital, Georgetown University Medical Center, Washington, District of Columbia, USA.
Am J Transplant ; 21(3): 1238-1254, 2021 03.
Article em En | MEDLINE | ID: mdl-32882110
ABSTRACT
Intestinal transplantation (ITx) can be life-saving for patients with advanced intestinal failure experiencing complications of parenteral nutrition. New surgical techniques and conventional immunosuppression have enabled some success, but outcomes post-ITx remain disappointing. Refractory cellular immune responses, immunosuppression-linked infections, and posttransplant malignancies have precluded widespread ITx application. To shed light on the dynamics of ITx allograft rejection and treatment resistance, peripheral blood samples and intestinal allograft biopsies from 51 ITx patients with severe rejection, alongside 37 stable controls, were analyzed using immunohistochemistry, polychromatic flow cytometry, and reverse transcription-PCR. Our findings inform both immunomonitoring and treatment. In terms of immunomonitoring, we found that while ITx rejection is associated with proinflammatory and activated effector memory T cells in the blood, evidence of treatment efficacy can only be found in the allograft itself, meaning that blood-based monitoring may be insufficient. In terms of treatment, we found that the prominence of intra-graft memory TNF-α and IL-17 double-positive T helper type 17 (Th17) cells is a leading feature of refractory rejection. Anti-TNF-α therapies appear to provide novel and safer treatment strategies for refractory ITx rejection; with responses in 14 of 14 patients. Clinical protocols targeting TNF-α, IL-17, and Th17 warrant further testing.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores do Fator de Necrose Tumoral / Rejeição de Enxerto Tipo de estudo: Etiology_studies / Guideline Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores do Fator de Necrose Tumoral / Rejeição de Enxerto Tipo de estudo: Etiology_studies / Guideline Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article